Genome-wide plasma cell-free DNA methylation profiling in pancreatic cancer patients using MeDIP-seq
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Pengxiao Li
PROVIDER: E-MTAB-9678 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:As a non-invasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma is raising increasing interest due to its diagnostic and biology applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. Through enriching methylated cfDNA fragments with MeDIP followed by deep sequencing, we aimed to characterize cfDNA methylome in cancer patients. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. MEDIPS package was used for the identification of differentially methylated regions (DMRs) between patients and normal ones. Overall, we identified 330 differentially methylated regions (DMRs) in gene promoter regions, 33 hypermethylation and 297 hypomethylation respectively, by comparing lung cancer patients and healthy individuals as controls. The 33 hypermethylation regions represent 32 genes. Some of the genes had been previously reported to be associated with lung cancers, such as GAS7, AQP10, HLF, CHRNA9 and HOPX. Taken together, our study provided an alternative method of cfDNA methylation analysis in lung cancer patients with potential clinical applications.
2019-03-31 | E-MTAB-7163 | biostudies-arrayexpress
Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness. DNA methylome analysis of pooled Human, Chimpanzee and Macaque
2014-02-01 | E-GEOD-48942 | biostudies-arrayexpress
Project description:Purpose: Generate genome-wide methylation profiles of non-small cell lung carcinomas (NSCLC) and their matching lung tissues for detection of hypermethylated and hypomethylated regions present in the tumors. Methods: MethylCapture followed by next-generation sequencing (Illumina GAIIx) of 7 nsclc tumor samples and paired lung tissues in replicated, plus one cell line, 2 fully artificially methylated and 2 fully artificially unmethylated controls. Normalization of methylation reads based on CpG coupling factor–method. Relative methylation scores (rms) in 500bp non-overlapping windows. 90th percentile of rpm (reads per million) values for all 500bp genome-wide windows, with rpm <1.33 were considered. Distributions of 10bp bins rms values within each 500bp genomic region were compared using both one-sided Student’s t-test and one-sided Wilcoxon rank-sum test. Testing was done separately for hypo- and hypermethylation and p-value threshold of 10-18. Results: MethylCap-seq data revealed strong positive correlation between replicate experiments and between paired tumor/lung samples. 14472 differentially methylated regions (DMR) with non-overlapping 500 bp windows were found. 57 DMRs were present in all NSCLC tumors. 287 were unique for squamous-cell carcinomas and 26 unique for adenocarcinomas. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. Conclusion: We provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC. The DMRs can be in further studies to develop sensitive biological markers for NSCLC, which may enable non-invasive diagnosis and early detection of the disease, and potentially allow histological classification. MethylCap-seq of 7 nsclc tumor samples and paired lung tissues, plus 2 fully methylated and 2 fully unmethylated controls.
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Project description:MethylCap-seq was performed to characterize the genome-wide DNA methylation in CLBL-1 8.0, a doxorubicin-resistant cDLBCL cell line, and CLBL-1 as control, and aimed to investigate underlying mechanisms of doxorubicin resistance in cDLBCL. Strong difference in methylation pattern of both promoter and gene-body regions was detected between CLBL-1 8.0 and CLBL-1. Methylated peaks with fold-change greater than 4 and a P value of less than 0.01 were defined as differentially methylated regions (DMRs); there were a total of 20289 hypermethylated and 38362 hypomethylated DMRs detected. Among these, 1339 hypermethylated and 4861 hypomethylated DMRs were in promoter regions, while 12855 hypermethylated and 18904 hypomethylated DMRs were in gene-body regions. There were 6.6% hypermethylated DMRs located on the promoter regions. A high percentage (63.4%) of hypermethylated DMRs were distributed within the gene body, and 7.8%, 5.1% and 23.8% hypermethylated DMRs were found to be clustered in upstream, downstream, and intergenic regions, respectively.
2020-10-22 | GSE149925 | GEO
Project description:The aim of the present study was to identify novel DNA methylation markers in bladder cancer (BCa) through genome-wide profiling of bladder cancer cell lines and subsequent MSP screening in urine samples. Experimental Design: MBD methylCap/seq was carried out to screen differentially methylated CpG islands using two BCa cell lines (5637 and T24) and two normal bladder mucosa (BM) samples. The top one hundred most hypermethylated targets were screened using Methylation Specific PCR (MSP) in small and big cohort of urine samples from BCa patients and normal controls. The diagnostic performance of the gene panel was further evaluated in different clinical scenarios. Results: In total, 1,627 gene promoter regions hypermethylated in BCa cell line were identified in genomic level methylation profiling. The followed screening procedure in clinical urine sample generated eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) capable of differentiating BCa from normal control. Subsequent validation in a large sample size enabled the optimisation of 5 methylation targets (VAX1, KCNV1, TAL1, PPOX1 and CFTR) for BCa diagnosis with sensitivity and specificity of 86.32% and 87.13%, respectively. In addition, VAX1 and LMX1A methylation could predict the tumour recurrence. Conclusions: Tumor specific biomarkers of BCa could be established by first performing genome level methylation profiling with cell lines and then screening the potential targets in urine samples. The panel of methylated genes identified was promising for the early non-invasive detection and surveillance of BCa. MBD methylCap/seq was carried out to screen differentially methylated CpG islands using two BCa cell lines (5637 and T24), and two normal bladder tissue mix as control.
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Project description:Aberrant CpG methylation is a universal trait of cancer cell genomes and can result in epigenetic modulation of gene activity; however, at which stages tumour-specific epigenetic patterns arise is unknown. Here, we analyse the methylome of APCM in mouse intestinal adenoma as a model of intestinal cancer initiation, and inventory a map of over 13,000 adenoma-specific recurrent differentially methylated regions (DMRs). We find that multiple genes coding for Polycomb proteins are upregulated in adenoma, and concomitantly, hypermethylated DMRs form preferentially at Polycomb target sites. We establish that DMRs are absent from proliferating intestinal epithelial cells or intestinal stem cells, and thus arise de novo after loss of APC. Importantly, a core set of DMRs is conserved in human colon cancer, defining a class of early epigenetic alterations that are distinct from known sets of epigenetically silenced tumour suppressors. The data presented suggests a sequence of events that leads to an altered methylome of colon cancer cells, and may allow more specific selection of clinical epigenetic biomarkers. Analysis of the methylome and RNA expression in adenoma of Apc-Min/+ mutant mice and of normal intestine in Apc-Min/+ and Apc-+/+ wild type mice.
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